In an open study, 17 patients (16 women, 1 man) with refractory or severe rheumatoid arthritis were treated with thalidomide. Two withdrew from the study in the first weeks. Thirteen patients received 531 +/- 63 mg/day of thalidomide for 18.8 +/- 8.8 weeks; in 2 the dose was 300 mg/day during 62 and 65 weeks. Seven patients attained complete remission, 5 partial remission, and the last 3 no improvement at all. Remissions lasted 6 years in 1 patient, 2 years in 3, 1 year in one, and varied between 8 months and 8 weeks in 7. After relapse, 5 patients received a 2nd course of treatment and attained remission again. This lasted 24, 10, and 9 months in 3; two are taking 100 mg/day of thalidomide as a maintenance dose and remain asymptomatic after 36 and 30 months. The side effects were drowsiness, constipation, hard swelling of the lower limbs, erythema of the face and limbs with local pruritus or burning sensation, hair loss, cough, nasal obstruction, fever, and skin and mucosal dryness. In 8 patients there was mild eosinophilia (less than 10%) and in 2 leukopenia. A 33-year-old woman showed amenorrhea up to 2 months after stopping treatment. After a 2nd course of treatment, 2 patients developed peripheral sensory neuropathy, which resolved spontaneously in 6 months. We believe these findings justify controlled trials with this agent.